Abstract

Background/Aim: Sequential treatment with targeted agents is standard of care for patients with metastatic renal cell carcinoma (mRCC). However, clinical data directly comparing treatment outcomes with a mammalian target of rapamycin inhibitor or a vascular endothelial growth factor-targeted agent in the second-line setting are lacking. We evaluated sequential treatment in a syngeneic, orthotopic mouse model of mRCC. Materials and Methods: BALBIc mice were orthotopically implanted with murine RCC (RENCA) cells expressing luciferase and randomized to vehicle, sunitinib, sunitinib followed by sorafenib, or sunitinib followed by everolimus. Tumor growth and metastases were assessed by in vivo (whole body) and ex vivo (primary tumor, lung, liver) luciferase activity and necropsies, performed on day 20 or 46 for vehicle and treatment groups, respectively. Results: Sunitinib followed by everolimus was associated with reduced luciferase activity and primary tumor weight and volume compared with sunitinib, and sunitinib followed by sorafenib. Conclusion: Sequential therapy with sunitinib followed by everolimus demonstrated significant antitumor and anti-metastatic effects.

ISI Document Delivery No.: 972CO
Times Cited: 0
Cited Reference Count: 28
Larkin, James Esser, Norbert Calvo, Emiliano Tsuchihashi, Zenta Fiedler, Ulrike Graeser, Ralph Kim, Dennis
Novartis Pharmaceuticals; Novartis; Pfizer
Funding was provided by Novartis Pharmaceuticals.J. Larkin has served M a consultant/ advisory role for Novartis, Pfizer, Bayer, AVEO, and GlaxoSmithKline, and has received research funding from Novartis and Pfizer. E. Calvo has served in a consultant/ advisory role for Novartis and Pfizer, and has received honoraria and research funding from Novartis and Pfizer. D. Kim and Z. Tsuchihashi are current/past employees of Novartis.
Int inst anticancer research
Athens
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